DNA base-pair mismatches arise during the course of genetic recombination and replication as a consequence of enzymatic errors or DNA damage. In the cell, there exist systems exist capable of recognizing and correcting these mistakes. In certain diseases, particularly cancer, these repair systems fail and mismatches persist in a diseased cell's DNA. Therefore, providing compounds and methods designed to recognize site specific mismatches in DNA is important for genetic screening and for the design of new chemotherapeutics.
Because many human diseases arise by single base pair changes in genes, the analysis of base pair mismatches and mutation has important implications in biomedical research and in medicine. For example, a considerable number of human genetic diseases are known to be caused by point mutation.
Existing methods designed for achieving such goals include assays using isolated mismatch recognition proteins, hybridization of oligonucleotide-fluorescent probe conjugates, electrophoretic/DNA chip methods, and differential chemical cleavage with reagents assaying for base accessability either in solution or the solid phase. None of these methods are ideal for detection of mismatches in the laboratory, and no strategies exist for using the presence of base-pair mismatches as a way of selectively treating disease.
Accordingly, there is a need for compositions and methods useful for recognizing site specific base-pair mismatches in polynucleotide duplexes.